Glycogenolysis and Glycogenesis

Glycogenesis and


       At the end of this lecture, student
will be able to

      Explain the reactions of glycogenesis

      Explain the reactions of

the regulation of glycogenesis & glycogenolysis

glycogen storage diseases


       Glycogen is the storage form of
glucose in animals, as starch in plants

       Quantity of glycogen in muscle
(250g) is 3 times higher than liver (75g)

       Glycogen is stored as granules in
the cytosol, where enzymes of glycogen synthesis and break down are present

       Prime function of glycogen (liver)
is to maintain the blood glucose levels, particularly and glycogen (muscle)
serves as a fuel reserve for the supply of ATP during muscle contraction

       synthesis of glycogen from glucose

       Takes place in the cytosol and
requires ATP and UTP, besides glucose

Reactions of Glycogenesis

  1. Synthesis of UDP-glucose:

       Hexokinase (muscle) &
glucokinase (liver)
glucose to glucose 6-phosphate

       Phosphoglucomutase catalyses the
conversion of glucose 6-phosphate to glucose 1-phosphate

       glucose 1-phosphate reacts with
UTP(Uridine triphosphate) to form uridine diphosphate glucose-UDPG catalysed by
the enzyme


Requirement of primer to initiate glycogenesis

       A small fragment of pre-existing
glycogen act as a ‘prime  to initiate
glycogen synthesis

       In absence of glycogen primer, a
specific protein namely ‘glycogenin‘ can accept glucose from UDPG

       Hydroxyl group of amino acid
tyrosine of glycogenin is the site at which the initial glucose unit is

       Enzyme glycogen initiator synthase
transfers the first molecule of glucose to glycogenin. Then glycogenin itself
takes up a few glucose residues to form a fragment of primer which serves as an
acceptor for the rest of the glucose molecules

Glycogen synthesis by glycogen synthase:

       Glycogen synthase is responsible for
formation of 1,4-glycosidic linkages, this enzyme transfers the glucose from
UDP-glucose to the non-reducing end of glycogen to form
α-1,4 linkages

Formation of branches in glycogen:

       Glycogen synthase can catalyse the
synthesis of a linear unbranched molecule with 1,4
αglycosidic linkages

       Glycogen is a branched tree-like

       Formation of branches is brought
about by the action of a branching enzyme, namely amylo 1,4-1,6

       This enzyme transfers a small
fragment of 5 to 8 glucose residues from the non-reducing end of glycogen chain
(by breaking α-1,4 linkages) to another glucose residue where it is linked by
α-1,6 bond

       This leads to the formation of a new
non-reducing end, besides the existing one

       Glycogen is further elongated and
branched, respectively by the enzymes glycogen synthase and glucosyl 4-6

overall reaction of the glycogen synthesis:

                (Glucose)n + Glucose + 2ATP
→(Glucose)n+1+ 2ADP+Pi

Out of 2
ATP, 1 is required for the phosphorylation of glucose while the other is needed
for conversion of UDP to UTP


       Degradation of stored glycogen in
liver and muscle constitutes glycogenolysis

       It is a irreversible process and
enzymes for this are present in cytosol

       Glycogen is degraded by breaking
α-1,4- &
α-1,6-glycosidic bonds

1. Action
of glycogen phosphorylase:
α-1,4-glycosidic bonds are cleaved
sequentially by the enzyme glycogen phosphorylase to yield glucose 1-phosphate

       This process – phosphorolysis,
continues until four glucose residues remain on either side of branching point
α-1,6-glycosidic link)

       Glycogen so formed is known as limit
dextrin which cannot be further degraded by phosphorylase

2. Action
of debranching enzyme:

       The branches of glycogen are cleaved
by two enzyme activities present on a single polypeptide called debranching
enzyme, hence it is a bifunctional enzyme

       Clycosyl 4 : 4 translerase activity removes a fragment of three
or four glucose residues attached at a branch and transfers them to another

       Here, one α-1,4-bond is cleaved and the same α-1,4 bond is made

       Amylo α-1,6-glucosidase breaks the α-1,6 bond at the branch with a single
glucose residue and releases a free glucose

       The remaining molecule of glycogen
is again available for the action of phosphorylase and debranching enzyme to
repeat the reactions stated above

Formation of glucose 6-phosphate and glucose:

       Combined action of glycogen
phosphorylase and debranching enzyme, glucose 1-phosphate and free glucose in a
ratio of 8:1 are produced

       G-1-phosphate is converted to
G-6-phosphate by the enzyme phosphoglucomutase

       G-6-P is converted to glucose in the
liver by the enzyme glucose -6- phosphatase

Regulation of glycogenesis and

       The regulation is essential to
maintain the blood glucose levels

       Glycogenesis and glycogenolysis are
controlled by the enzymes glycogen synthase and glycogen phosphorylase

of these enzymes is accomplished by 3 mechanisms

                                1. Allosteric

                                2. Hormonal

                                3. lnfluence of

1. Allosteric regulation of glycogen metabolism

       Certain metabolites that
allosterically regulate the activities of glycogen synthase and glycogen

       Control is carried out in such a way
that glycogen synthesis is increased when substrate availability and energy
levels are high

       On the other hand, glycogen
breakdown is enhanced when glucose concentration and energy levels are low


Hormonal regulation of glycogen metabolism:

       Hormones are also regulate glycogen
synthesis ad degradation

Regulation of glycogen synthesis by cAMP:

       The glycogenesis is regulated by
glycogen synthase

       Enzyme exists in two forms glycogen
synthase-a, which is not phosphorylated and the active form and secondly glycogen
synthase-b, which is phosphoryIated and inactive form

       Glycogen synthase-a can be converted
to b form by phosophorylation

       Process of phosphorylation is
catalysed by a cAMP dependent
protein kinase

       Inhibition of glycogen synthesis
brought by epinephrine and glucagon through cAMP by converting active glycogen
synthase ‘a’ to inactive synthase-b

Regulation of glycogen
degradation by cAMP:

       Hormones like epinephrine and
glucagon bring about glycogenolysis by their action on glycogen phosphorylase
through cAMP

       Glycogen phosphorylase exists in two
forms, active ‘a’ form and inactive ‘b‘ form

Effect of Ca2+ ions on

       When the muscle contracts, Ca2+
ions are released from sarcoplasmic reticulum

       Ca2+ binds to calmodulin-
calcium modulating protein and directly activates phosphorylase kinase without
the involvement of cAMP dependent protein kinase

       Therefore, insulin increased
glycogen synthesis and glucogon increase glycogen degradation

Glycogen storage diseases


       Glycogenesis is synthesis of
glycogen from glucose

       Degradation of stored glycogen
constitutes glycogenolysis

       Regulation of glycogen synthesis and
its degradation is accomplished by, Allosteric regulation, Hormonal regulation
& lnfluence of calcium

storage diseases are Von’s Gierke’s diseases, Pompe’s diseases, Cori’s
diseases, Anderson’s diseases, Mc Ardle’s diseases, Her’s diseases and Tarui’s

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